Department of Biomedical Engineering, Schools of Medicine and Engineering, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Comprehensive Cardiovascular Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2024 Jun 18;19(6):e0293105. doi: 10.1371/journal.pone.0293105. eCollection 2024.
Obg-like ATPase 1 (OLA1) protein has GTP and ATP hydrolyzing activities and is important for cellular growth and survival. The human OLA1 gene maps to chromosome 2 (locus 2q31.1), near Titin (TTN), which is associated with familial dilated cardiomyopathy (DCM). In this study, we found that expression of OLA1 was significantly downregulated in failing human heart tissue (HF) compared to non-failing hearts (NF). Using the Sanger sequencing method, we characterized the human OLA1 gene and screened for mutations in the OLA1 gene in patients with failing and non-failing hearts. Among failing and non-failing heart patients, we found 15 different mutations in the OLA1 gene, including two transversions, one substitution, one deletion, and eleven transitions. All mutations were intronic except for a non-synonymous 5144A>G, resulting in 254Tyr>Cys in exon 8 of the OLA1 gene. Furthermore, haplotype analysis of these mutations revealed that these single nucleotide polymorphisms (SNPs) are linked to each other, resulting in disease-specific haplotypes. Additionally, to screen the 254Tyr>Cys point mutation, we developed a cost-effective, rapid genetic screening PCR test that can differentiate between homozygous (AA and GG) and heterozygous (A/G) genotypes. Our results demonstrate that this PCR test can effectively screen for OLA1 mutation-associated cardiomyopathy in human patients using easily accessible cells or tissues, such as blood cells. These findings have important implications for the diagnosis and treatment of cardiomyopathy.
Obg-like ATPase 1 (OLA1) 蛋白具有 GTP 和 ATP 水解活性，对细胞生长和存活至关重要。人类 OLA1 基因位于染色体 2（2q31.1 位点），靠近肌联蛋白（TTN），后者与家族性扩张型心肌病（DCM）相关。在本研究中，我们发现与非衰竭心脏（NF）相比，衰竭人心肌组织（HF）中 OLA1 的表达显著下调。我们使用 Sanger 测序方法对人类 OLA1 基因进行了特征描述，并在衰竭和非衰竭心脏患者中筛选 OLA1 基因突变。在衰竭和非衰竭心脏患者中，我们在 OLA1 基因中发现了 15 种不同的突变，包括 2 种转换、1 种取代、1 种缺失和 11 种转换。除了一个非同义的 5144A>G，导致 OLA1 基因外显子 8 中的 254Tyr>Cys 外，所有突变均为内含子突变。此外，对这些突变的单倍型分析表明，这些单核苷酸多态性（SNP）彼此连锁，导致疾病特异性单倍型。此外，为了筛选 254Tyr>Cys 点突变，我们开发了一种具有成本效益、快速的遗传筛选 PCR 测试，可以区分纯合子（AA 和 GG）和杂合子（A/G）基因型。我们的结果表明，该 PCR 测试可以使用易于获得的细胞或组织（如血细胞），有效筛查人类患者中与 OLA1 突变相关的心肌病。这些发现对心肌病的诊断和治疗具有重要意义。
